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Biomedical subjects

Y Ikada

Publications and source records attributed to Y Ikada.

At least 217 records · Page 12Linked to original sources

Evaluation of a bilayer artificial skin capable of sustained release of an antibiotic.

A bilayer artificial skin, composed of an upper silicone sheet and a lower collagen sponge, has been developed by modifying a technique proposed by Yannas and Burke. We have applied it clinically with success, but infection sometimes occurred in the area where the artificial skin was placed. To use it safely in an infected wound, we developed a new type of artificial skin capable of sustained release of antibiotic. Microspheres of poly-L-lactic acid containing an antibiotic, were installed in the upper silicone sheet. The usefulness of the new type of artificial skin was suggested by in vitro studies.

Biocompatible Materials↗

Solidifying liquid with novel initiation system for detachable balloon catheters.

In endovascular surgery, to permanently hinder blood inflow into an aneurysm for example, a catheter is percutaneously introduced into an artery and the balloon is positioned and inflated by a solidifying liquid and then released into the diseased part. A novel solidifying liquid for the inflated balloon curable under the continuous feeding of oxygen through the wall of the balloon is described here. Glucose oxidase which oxidizes glucose producing hydrogen peroxide was used for polymerization of the solidifying liquid. This solidifying liquid cured even in the presence of oxygen and water. It was radiopaque when mixed with the iodinated X-ray contrast chemical iopamidol. In addition, the solidified liquid had appropriate mechanical properties. The endovascular surgery could be carried out safely using it.

Catheterization↗

Degradation of collagen suture in vitro and in vivo.

In vitro and in vivo degradation of collagen suture was investigated focussing on the change in the mechanical properties and weight. The in vitro hydrolysis was carried out for catguts using collagenase (pH 7.4) and pepsin (pH 1.6), simulating the in vivo environments. The kinetic study on the weight loss of the fibre at the collagenase hydrolysis suggested that the degradation proceeded gradually from the surface of the fibre into the core. The enzymatic hydrolysis was different from the non-enzymatic acidic hydrolysis which resulted in almost homogeneous degradation throughout the cross-section of the fibre from the beginning of the hydrolysis reaction. The rate of weight loss with enzymatic hydrolysis was in good agreement with that predicted under the assumption of continuous erosion from the surface. When the collagen sutures were implanted in the subdermal tissue of rabbits, severe infiltration of macrophages and neutrophils was observed at 4 wk post-implantation, probably because of the degradation products from the implanted sutures. Comparison of the tensile strength decrease with the weight loss observed at the in vivo degradation revealed that enzymatic and non-enzymatic hydrolysis occurred concurrently in the subcutaneous tissue.

Animals↗

Controlled cisplatin delivery system using poly(D,L-lactic acid).

Cisplatin (CDDP)-containing poly(D,L-lactic acid) microspheres (CDDP-MS) and beads (CDDP-B) with an average molecular weight of the oligomer of 1.2 x 10(4) and 4% CDDP loading were prepared. In Tris buffer, 95% of CDDP disappeared from CDDP-MS within 3 d. In vitro and in vivo, CDDP-B released CDDP for 30-57 d, and for 21-42 d, respectively. The other CDDP-B with an average oligomer molecular weight of 9.6 x 10(3) with 5% lactic acid monomers, that contained 4% CDDP, showed a two-phase CDDP release pattern and CDDP disappeared within 41 d in vitro, and within 21 d in vivo. Histologically, tissue necrosis surrounding the CDDP-B was not severe.

Animals↗

In vitro evaluation of biocompatibility of surface-modified poly(methyl methacrylate) plate with rabbit lens epithelial cells.

Collagen type I was immobilized onto a poly(methyl methacrylate) (PMMA) plate by covalent bonding following surface modification by two methods. One method introduced amino groups by aminolysis with N-lithioethylenediamine (PMMA-NH2) and the other introduced carboxyl groups by graft copolymerization of acrylic acid (AAc) and acrylamide (AAm) (PMMA-COOH). Lens epithelial rabbit cells were cultured on the PMMA plate which was immobilized with collagen. Polygonal cells with a mosaic appearance were observed on the PMMA-COOH plate immobilized with collagen type I, whereas pleomorphic cells were present on the virgin PMMA and on the PMMA-NH2 plate immobilized with collagen type I. We concluded the PMMA-COOH plate immobilized with collagen type I provided a more comfortable atmosphere for lens epithelial cells, causing no metaplasia, than the other plates used in this cell culture model experiment.

Animals↗

Effects of nicardipine on tube formation of bovine vascular endothelial cells in vitro.

BACKGROUND AND PURPOSE: The purpose of this study was to assess the effect of nicardipine, a Ca2+ channel blocker, on angiogenesis in vitro. METHODS: Bovine carotid artery endothelial cells were cultured between type I collagen gel layers with 10(-9) to 10(-5) M nicardipine. The morphological changes were monitored by phase-contrast microscopy and photographed. The total length of tubular structures was measured with an image analyzer system. Endothelial proliferation and migration assays were also performed with the same doses of nicardipine. RESULTS: Cultured endothelial cells form tubular structures between collagen gel layers. Tube formation of endothelial cells was suppressed by culture with 10(-9) to 10(-5) M nicardipine in a dose-dependent manner. Migration of endothelial cells was also suppressed by the same doses of nicardipine. However, proliferation of endothelial cells was not enhanced. CONCLUSIONS: Nicardipine acts as an inhibitor of angiogenesis in vitro by inhibiting the migration of endothelial cells. This result suggests that nicardipine may have therapeutic potential in angiogenic disorders such as tumor growth, atherogenesis, and diabetic retinopathy.

Animals↗

Rapid morphological changes in bovine brain microvascular endothelial cells on extracellular matrices.

The morphological changes in endothelial cells derived from bovine brain microvasculature, carotid artery, and aorta during growth on extracellular matrices were compared. All cells formed tubular structures on a basement membrane. Ultrastructural studies showed that the tubular structures had lumens surrounded by many endothelial cells. On type I collagen gel, brain microvascular endothelial cells still formed tubular structures, but the other two cell types formed confluent monolayers. However, when a second layer of collagen gel was laid over these cells, tubular structures developed within 2-3 days. Brain microvascular endothelial cells form tubular structures more readily than endothelial cells derived from large vessels on both basement membrane and type I collagen gel.

Animals↗

[Rapid morphogenesis of brain microvascular endothelial cells in culture system].

Endothelial cells of bovine brain microvascular vessels (BBECs), carotid artery (BCECs) and aorta (BAECs) were cultured on type I collagen and Matrigel. BBECs make tubular structures and BCECs and BAECs grow and make confluent monolayer on type I collagen gel. But BCECs and BAECs make tubular structures when second layer was overlaid. BBECs, BCECs and BAECs make tubular structures on Matrigel. These morphological changes were not affected by basic fibroblast growth factor. These results suggest that BBECs have more potent angiogenic ability than BCECs and BAECs.

Animals↗

Biodegradable microspheres containing adriamycin in the treatment of proliferative vitreoretinopathy.

The use of biodegradable polymer microspheres containing adriamycin for the treatment of proliferative vitreoretinopathy (PVR) in an experimental rabbit model was investigated. A single injection of microspheres containing 10 micrograms of adriamycin effectively decreased traction retinal detachment to 10% (n = 10), whereas 50% of eyes injected with blank microspheres (n = 10) developed retinal detachment (P < 0.05). A single injection of microspheres, containing 3 micrograms of adriamycin, did not suppress retinal detachment. Electroretinographic and histologic studies confirmed that the 10 micrograms injection of adriamycin in microspheres was not toxic to the retina, although the injection of the same amount of free adriamycin caused retinal necrosis and detachment. Thus, microspheres containing adriamycin hold promise as a new treatment modality for PVR.

Animals↗

Injectable microspheres with controlled drug release for glaucoma filtering surgery.

The authors evaluated the effects of biodegradable poly (lactic acid) microspheres that provided the controlled release of the antimetabolic agent adriamycin (ADR) to prevent post surgical fibrosis after glaucoma filtering surgery. Fifty six eyes of 28 rabbits underwent posterior lip sclerotomy and received a 0.2 ml subconjunctival injection that contained microspheres 90 degrees from the filtering site immediately after surgery. Microspheres containing ADR (100 or 200 micrograms) were randomly administered to one eye. The fellow eyes served as controls and received microspheres without the drug. Intraocular pressure in the eyes treated with the microspheres that contained the drug was significantly lower than that in the control eyes from days 7-12 in the 100 micrograms group and from days 6-16 in the 200 micrograms group (P < .05). Eyes that received ADR had a significantly longer patent filtering bleb compared with the control eyes (P < .05). No corneal complications were observed in the eyes treated with 100 micrograms of ADR and the control eyes. Peripheral corneal opacities (25%) and epithelial erosion (17%) were observed in the eyes that received the 200 micrograms dose, but the cornea returned to normal after 4 wk. These results suggest that controlled-drug-release microspheres with an antimetabolic agent may be promising for preventing fibrosis after surgery.

Animals↗

Clinical use of synthetic absorbable cuff material for peripheral vascular anastomosis.

End to end arteriovenous (AV) fistulas were created using the cuff technique for hemodialysis in 12 patients with end stage renal disease. The cuff used was made of a synthetic biodegradable material, a lactic glycolic acid co-polymer with the same composition as absorbable surgical suture. Cephalic vein radial artery fistulas in the forearm were created electively in six patients to convert a Scribner shunt to a fistula in three patients and because of malfunction of a fistula created previously in three patients. Eleven patients underwent hemodialysis, with pump speeds of more than 200 milliliters per minute, and were evaluated for 129 to 477 days. These subcutaneous AV fistulas were maintained as patent functional veins and continued to function without complication. After five weeks, one patient had conversion to a prosthetic AV fistula because of poor venous maturation. The overall patency rate was 92 percent. The diameter of the AV anastomosis increased gradually with time. At 20 weeks, however, it reached more than 70 percent of the diameter of the radial artery lumen. These observations led us to believe that the cuff material used is biodegraded until 20 weeks and gives sufficient flexibility. In the future, the cuff method is expected to be clinically developed as another approach for vascular anastomosis.

Adult↗

Isolation of adult pig islet. In vitro assessment and xenotransplantation.

This study was conducted to develop an isolation method for adult pig islets and to investigate in vivo function after xenotransplantation as well as in vitro function of isolated islets. From the splenic portion of the glands (n = 20), 3277 +/- 645 islets per gram of pancreas were isolated and recovered by a five-step dextran discontinuous density gradient method. Purity of the final preparation obtained from 20 different consecutive pig pancreata was 80-90%. In vitro incubation study revealed a significant insulin release from isolated adult pig islets in response to glucose stimulation. In vitro perifusion study demonstrated a biphasic insulin response to glucose stimulation from isolated islets. Xenotransplantation of approx 2000 isolated adult pig islets into the portal vein of diabetic Wistar rats (n = 8) significantly reduced serum glucose levels from 431 +/- 24 mg/dL to 173 +/- 18 mg/dL 24 h after transplantation. This study provides a development of an isolation method for adult pig islets and demonstrates that isolated islets are viable and functioning both in vitro study and in vivo study of xenotransplantation.

Animals↗

A study on elongation and knot slacking of various sutures.

The tension holding capacity of suture materials was measured by in vitro and in vivo experiments. Silk and expanded polytetrafluoroethylene sutures showed large elongation and significant knot slacking after tight tying. Although ultrahigh molecular-weight polyethylene suture had excellent creep resistance, it showed a relatively low tension holding capacity because of substantial knot slacking. On the other hand, polyester and high-strength poly(vinyl alcohol) sutures showed an excellent in vivo tension holding capacity, along with low elongation and insignificant knot slacking. Clinical performance of these sutures was briefly discussed from the mechanical point of view.

Elasticity↗

Effects of recombinant alpha-interferon-gelatin conjugate on in vivo murine tumor cell growth.

A recombinant human alpha-interferon A/D (IFN), also known to be effective in mice, was conjugated to gelatin with a water-soluble carbodiimide. The IFN-gelatin conjugate was much more efficient than free IFN in activating mouse peritoneal macrophages (Mø) in an in vitro experiment to inhibit the growth of IFN-resistant subline cells (RR1) of murine fibrosarcoma. A single i.p. injection of the conjugate administered to normal mice was also more effective than one of free IFN in activating peritoneal Mø and natural killer cells in peritoneal exudate cell and spleen cell populations. In the investigation on body distribution of the IFN-gelatin conjugate, an enhanced affinity to Mø as well as a prolonged retention were observed in comparison with free IFN. An injection of the IFN-gelatin conjugate i.p. was more effective than one of free IFN in suppressing the in vivo growth of not only IFN-sensitive SS2 cells but also RR1 cells in the peritoneal cavity of mice, although RR1 cells were only susceptible to the indirect effect of IFN via host cells, in contrast to SS2 cells. In addition to an increased recruitment of Mø to the peritoneal cavity in RR1-bearing mice receiving i.p. injection of the IFN-gelatin conjugate, these Mø were activated to inhibit the in vitro growth of RR1 cells. These results indicate that the IFN-gelatin conjugate is a promising antitumor agent that is much more effective than free IFN. The dose of IFN in the conjugate required for exerting the antitumor effects is much lower than that of free IFN, which leads to a reduction of adverse effects of IFN.

Animals↗

Biodegradable screw fixation of rabbit tibia proximal osteotomies.

The purpose of this study was to evaluate a biodegradable poly(L-lactide) (P-L-LA) screw for osteosynthesis under a load-bearing condition. A proximal tibial osteotomy on 25 rabbits was fixed with a biodegradable screw made of P-L-LA. A follow-up study was done at 1, 2, 4, 8, and 16 weeks. In another 25 rabbits, the tibial osteotomy was fixed with stainless steel (SUS) screws of the same size as the P-L-LA screws with a similar follow-up period. Radiographic, histological, microradiographic, and oxytetracycline-labeling studies showed healing of the osteotomy within 4 to 8 weeks. The displacement of fragments and the mass of newly formed bone around the screws were measured by histomorphometric analysis. There was no significant difference in the displacement of the fragments in these two groups and new bone was more abundantly detected in the P-L-LA group than in the SUS group. Histologically, no inflammatory lesion was detected in either group. All osteotomies united without delay and the displacement was minimal, although no external support was applied and the rabbits were allowed to move freely after the operation. The results of this study suggest a possible use for a P-L-LA screw in the clinical treatment of human bone fractures.

Animals↗

Poly(vinyl alcohol) hydrogel as an artificial articular cartilage: evaluation of biocompatibility.

We have developed a new poly(vinyl alcohol) hydrogel (PVA-H) of increased physical strength through a new manufacturing process. Its mechanical properties have been found to be preferable as a substitute for articular cartilage. To evaluate its biocompatibility as an artificial articular cartilage, a series of in vivo tests within the intraarticular, as well as the intramuscular, environment were conducted. Tissue reactions of cartilage, bone, synovium, and muscle to PVA-H were studied histologically. In the experimental group, in which PVA-H was implanted, inflammatory reactions of all of these tissues were very slight. In the control group, in which ultra-high molecular weight polyethylene (UHMWPE) was implanted, although tissue reactions of bone and muscle were as slight as in the experimental group, those of cartilage and synovium were somewhat more conspicuous. By way of these findings, the better biocompatibility of PVA-H was documented.

Animals↗

Collagen-immobilized hydrogel as a material for lamellar keratoplasty.

A transparent poly(vinyl alcohol) hydrogel disc covalently immobilized with Type I collagen, fibronectin, and an adhesive oligopeptide and preseeded with corneal epithelial cells was implanted in the rabbit cornea using a technique of lamellar keratoplasty, and the tissue response was studied by light and electron microscopy. Covalent immobilization of type I collagen on the surface of hydrogel was found to support growth and adhesion of the corneal epithelium in vitro. The in vivo experiment showed that cell seeding could prevent infection of the hydrogel. However, the implanted disc was rejected from the host cornea by epithelial downgrowth and the exchange between the seeded cells and host corneal epithelia was not observed until 14 days after surgery. The rejection might have occurred because of unsatisfactory fixation of the hydrogel to the host cornea.

Animals↗